A study to compare the change in cognitive performance and psychological status of patients with spasticity due to Multiple Sclerosis when treated with Sativex or placebo, added to existing anti-spasticity therapy over a period of 48 weeks. Secondary objectives were to evaluate the effect of Sativex on mood and spasticity and to assess the safety and tolerability of Sativex.
BACKGROUND: The long term impact of a newly approved cannabisbased THC.:CBD oromucosal spray on cognitive function and mood was a safety concern at the time of its approval as a treatment for spasticity due to multiple sclerosis (MS). This study was done as part of the risk management plan agreed between European regulatory agencies. This is the first report of the results. METHODS: Patients with moderate to severe spasticity despite treatment with other anti-spasticity agents were randomised to receive THC.:CBD or matching placebo for 12 months. The primary endpoint was the comparison between active and placebo in the change from baseline to end of study in the Paced Auditory Serial Addition Test 2 and 3 (PASAT). Secondary endpoints included the Beck Depression Inventory-II (BDI-II), the subject, physician and caregiver global impression of change (GIC), the Columbia Suicidality Severity Rating Scale. RESULTS: 121 subjects were randomised. Mean age was 49 years (SD = 9.6); mean duration of MS was 13.9 years (SD = 8.6). The female:male ratio was 63:37%. Mean exposure duration in the THC.:CBD group was 294 days compared with 300 days in the placebo group. Concomitant anti-spasticity medication included baclofen in 54%, tizanidine in 18%, benzodiazepines in 30%, gabapentinoids in 18%. 49% of subjects had relapsing-remitting, and 39% secondary progressive MS. Baseline PASAT score in the active group was 59.4 and in the placebo group was 62.1. After 12 months, the mean change was +6.8 in both groups. The change in the BDI-II score was -3.1 in the active group compared with -2.4 in the placebo group. Neither difference approached significance. Patient, physician and caregiver GIC were all significantly in favour of THC.:CBD (p<0.0001; p=0.0014; p=0.0042 respectively). Withdrawal from treatment occurred in 19% of subjects on both CBD.:THC and placebo. Overall, adverse events (AEs) were reported by 63% of subjects on CBD.:THC and 32% of subjects on placebo. AEs led to cessation of study medication in 11 subjects - 9 on active and 2 on placebo. 1 out of 5 reported serious AEs was related to THC.:CBD. There was one case of suicidal ideation, in a subject taking placebo. No psychotic disorders were reported. CONCLUSIONS: Long-term treatment with THC.:CBD spray is not associated with cognitive decline or significant changes in mood. Efficacy, assessed separately by the patient, physician and caregiver, is maintained in long-term treatment.
OBJECTIVE: When Sativex® THC/CBD cannabinoid-based oromucosal spray was first approved as a prescription medicine for multiple sclerosis (MS) spasticity, there was some concern about its possible long-term impact on cognition and mood. The objective of this study was therefore to assess the long-term impact of Sativex on cognitive function and mood in MS patients with spasticity.
METHODS: 121 patients were randomly assigned Sativex or placebo in a double-blind manner. Patients selfadministered treatment daily for 48 weeks while maintaining anti-spasticity therapy. The primary endpoint was the difference between treatments in Paced Auditory Serial Addition Test (PASAT) score from baseline to end of treatment. Secondary measures included Beck Depression Inventory-II (BDI-II), Subject-, Physician- and Caregiver Global Impression of Change, and Columbia-Suicide Severity Rating Scale.
RESULTS: 62 patients were randomised to Sativex and 59 to placebo. There was no difference in the effect of Sativex on PASAT and BDI-II scores compared with placebo. Subject-, Physician- and Caregiver-rated improvements in spasticity with Sativex were all statistically significant. The mean daily dose of Sativex declined gradually to 6.4 sprays per day.
CONCLUSION: Long-term treatment with Sativex was not associated with cognitive decline or significant changes in mood in this prone population sample. Sativex was efficacious and well tolerated across the study period and no new safety concerns were identified.
A study to compare the change in cognitive performance and psychological status of patients with spasticity due to Multiple Sclerosis when treated with Sativex or placebo, added to existing anti-spasticity therapy over a period of 48 weeks. Secondary objectives were to evaluate the effect of Sativex on mood and spasticity and to assess the safety and tolerability of Sativex.
